Hopes, joys and fears: Meaning and perceptions of viral load testing and low-level viraemia among people on antiretroviral therapy in Uganda: A qualitative study

Uganda applies the World Health Organization threshold of 1,000 copies/ml to determine HIV viral non-suppression. While there is an emerging concern of low-level viraemia (≥50 to <1,000 copies/ml), there is limited understanding of how people on antiretroviral therapy perceive viral load testing and low-level viremia in resource-limited settings. This qualitative study used the health belief model to explore the meaning that people living with HIV attach to viral load testing and low-level viraemia in Uganda. We used stratified purposive sampling to select people on antiretroviral therapy from eight high volume health facilities from the Central, Eastern, Northern and Western regions of Uganda. We used an interview guide, based on the health belief model, to conduct 32 in-depth interviews, which were audio-recorded and transcribed verbatim. Thematic analysis technique was used to analyze the data with the help of ATLAS.ti 6. The descriptions of viral load testing used by the participants nearly matched the medical meaning, and many people living with HIV understood what viral load testing was. Perceived benefits for viral load testing were the ability to show; the amount of HIV in the body, how the people living with HIV take their drugs, whether the drugs are working, and also guide the next treatments steps for the patients. Participants reported HIV stigma, lack of transport, lack of awareness for viral load testing, delayed and missing viral load results and few health workers as the main barriers to viral load testing. On the contrary, most participants did not know what low-level viraemia meant, while several perceived it as having a reduced viral load that is suppressed. Many people living with HIV are unaware about low-level viraemia, and hence do not understand its associated risks. Likewise, some people living with HIV are still not aware about viral load testing. Lack of transport, HIV stigma and delayed viral load results are major barriers to viral load testing. Hence, there is an imminent need to institute more strategies to create awareness about both low-level viraemia and viral load testing, manage HIV related stigma, and improve turnaround time for viral load results.

First and foremost, we greatly and humbly thank you all for taking off time to carefully read our manuscript and giving us very insightful review comments. We greatly believe that addressing these comments has been very key in improving our manuscript. Thank you very much once again.
We hereby humbly submit the responses to the different review comments raised, as shown below;

ACADEMIC EDITOR
Thank you for submitting your manuscript to PLOS Global Public Health. After careful consideration, we feel that it has merit but does not fully meet PLOS Global Public Health's publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. a) Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article's retracted status in the References list and also include a citation and full reference for the retraction notice.
 Thank you very much for this very useful comment. We have read through the entire manuscript again carefully looking at every reference following your guidance. We have realized that some of the references had not been updated automatically by the referencing software, and hence we have updated them. A number of references including; 2, 11,12,13,30,31,33,34,36 and 37 have been updated to reflect the exact articles that they reference, as shown in the manuscript with track changes. We are sorry for this oversight, and we greatly thank you very much once again for noticing this oversight in the manuscript. Thank you very much.
b) Your manuscript is missing the following sections: Introduction. Please ensure these are present, and in the correct order, and that any references to subheadings in your main text are correct. An outline of the required sections can be consulted in our submission guidelines here: https://journals.plos.org/globalpublichealth/s/submission-guidelines#locparts-of-a-submission d) In the online submission form, you indicated that "The codebook for the study has been availed. Any further datasets used and/or analysed during the current study are available from the corresponding author on reasonable request". All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons by return email and your exemption request will be escalated to the editor for approval. Your exemption request will be handled independently and will not hold up the peer review process, but will need to be resolved should your manuscript be accepted for publication. One of the Editorial team will then be in touch if there are any issues.
 Thank you very much for this. We have addressed this in the online submission.

REVIEWER #1 General Comment
HIV management is one aspect of the field of medicine that has faced a lot of challenges. Initial challenges revolved around acceptance of HIV status, stigma, lack of support systems, and availability of ARVs especially in low and middle-income countries. Emerging challenges are issues to do with adherence to medication and the management of HIV in general. The author's findings on HIV patient perception towards VL testing is a plus in the management of HIV. The ability of PWH to interpret and appreciate the role of LLV in HIV management is a good sign of the acceptability of VL testing by the patients in their management. The conclusion of the study identify areas that needs improvement in the utilization of VL testing in the monitoring and management of HIV patients.

Major Points
a) To deal with sampling bias during participant selection, the authors should clarify if they include defaulters in their sample (pg 6).
 Thank you very much for this comment. It also actually raises ethical concerns and we have addressed this in Lines 132 to 133 on page 6. Thank you for raising this comment. Furthermore, we are also humbly informing you that we used stratified purposive sampling (as shown in Line 127 on page 6) to enable us get the participants who were fit to answer the study research questions in details. Thank you very much. b) One aspect of low-level viremia is misinterpretation and misuse of the LLV results by the patients themselves or by other support systems around the patients. How did the authors capture this challenge (pg 17-18)  Thanks for this comment, and it is actually an insightful challenge. However we discussed this challenge further in the discussion section, from Lines 502 to 508 on Page 21. Thank you very much.
c) Was culture a barrier to VL testing? (pg 14)  Thank you very much for this question. Of course, culture has always been a barrier, and several interventions like sensitization have been used to overcome it. In this study, we used an inductive approach, which involved hearing more from what the participants said, compared to what we knew (deductive approach). In the interviews, the participants talked about different myths, though some of them were not really related to culture as such. However we greatly agree with you that culture is still a barrier in HIV care, which needs to be investigated thoroughly well. f) It would have been better if the authors included the healthcare givers in their study population. Generally, healthcare provision is a collaborative effort between the patients and the clinicians.

Minor Points
 Thank you for noting this. The perceptions of health workers about LLV and VL testing would be great to include here. However the manuscript would be large, and the study team agreed to do this later on, and include it in another totally separate manuscript. Thank you very much.

REVIEWER #2
Nanyeenya et. al present a qualitative study based on the health belief model in which they assess the perceptions of HIV viral load testing and low-level viremia in people living with HIV in Uganda. This study provides unique insights into patient perceptions and understanding of viral load testing and results interpretation. Such studies are a crucial piece needed for developing more effective interventions to improve the overall care for people with HIV in a manner that centers their needs and enhances their understanding of these interventions. The manuscript is very well written and clearly presented. There are some comments the authors may wish to consider to improve on their work. a) In the discussion I would have liked to see the authors discuss how their results could be used to design interventions which can improve on how patients view low level viremia and even propose plausible interventions that could be effective based on the data they have generated.
 Thanks very much for raising this very critical comment. This has been addressed as shown in Lines 497 to 500, 529 to 530, and 532 to 534 in the discussion section. Once again, thank you for highlighting this comment.
b) I applaud the efforts made by the authors to methodically conduct detailed interviews adapted for language and cultural setting which is so crucial to obtain information that accurately represents the views of the respondents however the sample size (n=32 detailed interviews) of the study is quite small which makes one to wonder whether such a small sample size is sufficient to fully capture the full spectrum of perceptions among people living with HIV. Could the authors comment on this choice of sample size and acknowledge this limitation in the manuscript?
 Thank you very much for this comment. In order to make this study feasible, we estimated that a minimum of 32 in-depth interviews (IDIs) with PLHIV on ART would be conducted until information saturation was reached. This minimum sample size was estimated based on Saunders et al., (Saunders et al., 2018) and Guest et al., (Guest et al., 2006)  c) The authors present their results very well. A summary figure or table of the key themes emerging from the detailed interviews as detailed in the sub-headings in the results section will break the monotony of lengthy text and provide a nice summary of the findings to accompany the detailed reporting of the results.
 Thank you very much for this very insightful and critical comment. We have developed summary figure as per your guidance, as shown by the caption on Line 188 on page 8. The figure has also been saved and uploaded as Fig 1, as required by the Journal guidelines. d) Line 541minor typo correct behaviours currently spelled as bahaviors  Thank you very much for this. We have addressed it as shown in Line 546.
Once again, thank you very much for the comments.